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DEFECTS IN CERVICAL VERTEBRAE IN BORIC ACID-EXPOSED RAT EMBRYOS ARE ASSOCIATED WITH ANTERIOR SHIFTS OF HOX GENE EXPRESSION DOMAINS
Citation:
Wery, N., M G. Narotsky, N. Pacico, R J. Kavlock, J. J. Picard, AND F. Gofflot. DEFECTS IN CERVICAL VERTEBRAE IN BORIC ACID-EXPOSED RAT EMBRYOS ARE ASSOCIATED WITH ANTERIOR SHIFTS OF HOX GENE EXPRESSION DOMAINS. BIRTH DEFECTS RESEARCH PART A: CLINICAL AND MOLECULAR TERATOLOGY 67(1):59-67, (2003).
Description:
Defects in cervical vertebrae in boric acid-exposed rat embryos are associated with anterior shifts of hox gene expression domains
Nathalie Wery,1 Michael G. Narotsky,2 Nathalie Pacico,1 Robert J. Kavlock,2 Jacques J. Picard,1 AND Francoise Gofflot,1*
1Unit of Developmental Genetics, Universite catholique de Louvain, Bruxelles, Belgium
2U.S. Environmental Protection Agency, Reproductive Toxicology Division, Research Triangle Park, NC 27711, U.S.A.
ABSTRACT
Previously, we showed that prenatal exposure to boric acid (BA), an industrial agent with large production, causes alterations of the axial skeleton in rat embryos, reminiscent of homeotic transformations. Indeed, Sprague-Dawley rats exposed in utero to BA on gestation day nine (GD 9) had only six, rather than the normal seven, cervical vertebrae. This finding, observed in 91 % of GD 21 fetuses, suggests posterior transformations of vertebrae. The present study attempts to determine if these skeletal alterations could be explained by modifications of the hox code, involved in the establishment of positional information along the rostro-caudal axis of the embryo. Pregnant rats were treated by gavage with BA (500 mg/kg, twice) on GD 9. Embryos were collected on GD 11 or GD 13.5 and processed for in situ hybridization. Several hox genes were selected according to the position of their rostral limit of expression in the cervical and thoracic region. At GD 13.5, we detected a cranial shift of the rostral limit of expression of hoxc6 and hoxa6. We observed no difference between control and treated embryos in the location of the rostral limit of expression of the other genes: hoxd4, hoxa4, hoxc5 and hoxa5. Our results demonstrate that in utero exposure to BA on GD 9 results on GD 13.5 in a disturbance of the expression of hox genes involved in the specification of rostral vertebrae. The anteriorization of the expression of hoxc6 and hoxa6 can explain a posterior transformation of cervical vertebrae, in agreement with the phenotype observed in BA-exposed fetuses at GD 21.